The objective of this proposed research is to address specific deficiencies in our understanding of the chemical factors within contracting muscle that contribute to the reflex cardiovascular response to exercise. A better understanding of these factors may allow physicians to modify these responses where they may be harmful, for instance in patients with ischemic heart disease. The specific aims and methodologies are: 1) determination of the reflex potential of chemical stimuli released during muscular contraction. This will be accomplished by stimulating the cat's skeletal muscle with intra-arterial injections of each chemical to evoke a cardiovascular response. The reflex nature of the response will be confirmed by denervation of the gracilis. 2) Evaluation of the contribution of those chemical stimuli with reflex potential to the reflex cardiovascular response evoked by static muscular contraction. To evaluate the potential contribution of each chemical, the cardiovascular response to ventral root stimulated static contraction will be attenuated by inhibiting the production or action of the substance pharmacologically or by enhancing its degradation by infusing the appropriate enzyme responsible for catabolism. Alternatively, the degradation of a given chemical will be inhibited pharmacologically to demonstrate an augmented contraction-induced cardiovascular response. 3) Evaluation of the relationship between changes in interstitial PO2, PCO2 and pH to the onset and magnitude of the cardiovascular response to electrically stimulated contraction. To study this effect, skeletal muscle interstitial PO2, PCO2 and pH will be measured with mini-electrodes during contraction and contraction accompanied with ischemia. The time course and magnitude of changes in these variables will be compared to the onset and magnitude of the cardiovascular responses to contraction and contraction with ischemia. The cardiovascular response to pharmacological stimulation and hindlimb contraction will be evaluated by assessing changes in arterial blood pressure, heart rate and contractility. In some animals changes in preload, aortic flow and systemic vascular resistance also will be assessed.